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Mathematical model personalizes treatment.

Cancer chemotherapy can be a lifesaver, but it is fraught with severe side effects, among them an increased risk of infection. Until now, the major criterion for assessing this risk has been the blood cell count: if the number of white blood cells falls below a critical threshold, the risk of infection is thought to be high. A new model built by mathematicians at the Weizmann Institute of Science, Rehovot, Israel, in collaboration with physicians from the Meir Medical Center in Kfar Saba, Israel, and the Hoffmann-La Roche research center in Basel, Switzerland, suggests that, for proper risk assessment, it is essential to evaluate not only the quantity of these blood cells, but their quality, which varies from one person to another.

This research may represent an important step in the emerging field of personalized medicine, leading to a more individualized approach to chemotherapy. In particular, better precautions might need to be taken to prevent infection in high-risk patients whereas those at a low risk could be spared unnecessary preventive treatments.


The model reveals how the immune system functions under conditions of neutropenia--a dangerously how level of white blood cells, mainly neutrophils. In this condition, which often emerges after chemotherapy or a bone marrow transplant, severe infections can develop if the immune system fails to perform the crucial function of devouring and destroying bacteria.

The model suggests that, in neutropenia, the tug-of-war between blood cells and bacteria cannot be explained away by the simple bacteria to-cell ratio, nor by the threshold that the blood cell count must exceed. Rather, when neutrophil counts are low, the patient's immune system enters a fragile equilibrium--described as "bistabilit" in mathematical terms --which can be disrupted easily, with dramatic consequences, by even minute changes in bacterial concentration or neutrophil numbers.

Other factors that can affect this equilibrium radically include the effectiveness of the neutrophil functioning and the permeability of tissues to bacteria, which can increase due to cancer therapy.

The model already has offered a plausible explanation for a number of medical mysteries. It helps illuminate, for instance, why, after chemotherapy, some cancer patients contract life-threatening infections even when in isolation under sterile conditions: if the neutrophils of these patients are "weak," even the smallest numbers of bacteria--for example, those present in the gut--can tilt the fragile immune balance in favor of the bacteria.

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Title Annotation:Chemotherapy
Publication:USA Today (Magazine)
Geographic Code:7ISRA
Date:Feb 1, 2013
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